Leishmania infection leads to a large spectrum of human diseases some influenced by parasite strains and others more associated to the host immune response to the parasite. It is still unclear the mechanisms that induce the different immunological responses that lead to different clinical forms of leishmaniasis. Studies proposed in this application will investigate the role of parasite antigenic differences and shed light on host genetic differences influencing disease outcome resulting in cutaneous (CL), mucosal leishmaniasis (ML), or sub-clinical infection (SCL) after infection with a single Leishmania species. Studies proposed in Aim 1 will characterize the ability of genotypically different L. braziliensis isolates from patients with ML and CL to induce differential systemic immune responses in ML, CL and SCL patients. Aim 2 will perform begin family based association analyses of polymorphic candidate genes using data and DNA from an existing family study to begin to explore the host genetic contribution to disease outcome. The future impact of this research related to the studies of antigenic differences of parasite strains is its implications for vaccine development and immunotherapy. The identification of genetically susceptible subjects to develop severe forms of disease might help to direct more intense epidemiological control measures or a more careful therapy follow-up to these subjects. [unreadable] [unreadable] [unreadable]